title: Resveratrol regulates the cell viability promoted by 17β-estradiol or bisphenol A via down-regulation of the cross-talk between estrogen receptor α and insulin growth factor-1 receptor in BG-1 ovarian cancer cells.
abstract: Endocrine disrupting chemicals (EDCs) and estrogens appear to promote development of estrogen-dependent cancers, including breast and ovarian carcinomas. In this study, we evaluated the cell viability effect of BPA on BG-1 human ovarian cancer cells, along with the growth inhibitory effect of resveratrol (trans-3,4,5-trihydroxystilbene; RES), a naturally occurring phytoestrogen. In addition, we investigated the underlying mechanism(s) of BPA and RES in regulating the interaction between estrogen receptor alpha (ERα) and insulin-like growth factor-1 receptor (IGF-1R) signals, a non- genomic pathway induced by 17β-estradiol (E2). BPA induced a significant increase in BG-1 cell growth and up-regulated mRNA levels of ERα and IGF-1R. In parallel with its mRNA level, the protein expression of ERα was induced, and phosphorylated insulin receptor substrate-1 (p-IRS-1), phosphorylated Akt1/2/3, and cyclin D1 were increased by BPA or E2. However, RES effectively reversed the BG-1 cell proliferation induced by E2 or BPA by inversely down-regulating the expressions of ERα, IGF-1R, p-IRS-1, and p-Akt1/2/3, and cyclin D1 at both transcriptional and translational levels. Taken together, these results suggest that RES is a novel candidate for prevention of tumor progression caused by EDCs, including BPA via effective inhibition of the cross-talk of ERα and IGF-1R signaling pathways.
authors.affiliation: Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk 361-763, Republic of Korea.
authors.forename: Nam-Hee
authors.initials: NH
authors.lastname: Kang
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Hwang
authors.forename: Hye-Rim
authors.initials: HR
authors.lastname: Lee
authors.forename: Dal-Woong
authors.initials: DW
authors.lastname: Choi
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D001559:Benzhydryl Compounds / Q000037:antagonists & inhibitors / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004958:Estradiol / Q000737:chemistry / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D010636:Phenols / Q000037:antagonists & inhibitors / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D048789:Phytoestrogens / Q000494:pharmacology*; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000819:agonists / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D000098826:Bisphenol A Compounds
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001559:Benzhydryl Compounds; D019938:Cyclin D1; D004958:Estradiol; D047628:Estrogen Receptor alpha; D004968:Estrogens, Non-Steroidal; D055504:Insulin Receptor Substrate Proteins; D009363:Neoplasm Proteins; D010636:Phenols; D048789:Phytoestrogens; D017526:Receptor, IGF Type 1; D000077185:Resveratrol; D013267:Stilbenes; C530104:CCND1 protein, human; C506487:ESR1 protein, human; C526292:IRS1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds
keywords: Cell proliferation; ERα; Endocrine disrupting chemicals; IGF-1R; Resveratrol